Structural And Functional Brain Abnormalities In Cognitive Subtypes Of First-episode Schizophrenia

Background: Cognitive impairment in schizophrenia is highly heterogeneous.A growing body of evidence suggests that there are identifiable cognitive subtypes in schizophrenia with more homogeneous cognitive profiles,which provides an important entry point for understanding the mechanisms of cognitive impairment in schizophrenia.Our study aims to explore the cognitive subtypes of first-episode schizophrenia and reveal the differences in brain structure and spontaneous neural activity among different cognitive subtypes.Methods: Based on multicenter data,we screened 181 patients with first-episode schizophrenia and 107 healthy controls.Cognitive function was assessed by the MATRICS Consensus Cognitive Battery,and all subjects completed structural and resting-state functional magnetic resonance imaging scans.Latent profile analysis was used to identify cognitive subtypes in schizophrenia.One-way analysis of covariance was performed for gray matter volume(GMV)and amplitude of low-frequency fluctuations(ALFF)in cognitive subtypes and healthy controls,controlling age,sex,years of education,and TIV/head movement as covariables.Then,partial correlation analysis was used to explore the correlation between abnormal brain regions and cognition in schizophrenia.Results: Two cognitive function categories were identified,which were named as low cognitive group and high cognitive group.Both cognitive subtypes had decreased GMV in the right hippocampus.Compared to the control and high cognitive group,low cognitive group had decreased GMV in the right insula and left superior temporal gyrus.In addition,both cognitive subtypes had decreased ALFF in the right rectus and increased ALFF in the left caudate nucleus compared to healthy controls,whereas there was no difference between subtypes.Compared to the control and low cognitive group,high cognitive group had decreased ALFF in the left medial orbital gyrus and left inferior frontal gyrus-opercular part.Compared to the control and high cognitive group,low cognitive group had decreased ALFF in the left precuneus and right angular gyrus.Correlation analysis showed that insular,superior temporal gyrus,and inferior frontal gyrus-opercular part were correlated with multiple cognitive domains.Conclusions: We observed GMV deficits and regional dysfunction in cognitive subtypes,mainly distributed in the fronto-temporo-limbic system.The insula,superior temporal gyrus,and inferior frontal gyrus-opercular part were associated with multiple cognitive domains.These findings may help to further understand the pathophysiological mechanisms of cognitive dysfunction in schizophrenia.